The potential impact of antioxidants on aging and degenerative diseases has been widely recognized in recent years and billions of dollars are spent annually on megadose antioxidant supplements. The modem free radical theory of aging postulates a shift in the antioxidant/pro-oxidant balance that leads to increased oxidative stress, dysregulation of cellular function, and aging. In the context of this theory, antioxidants can influence the primary "intrinsic" aging process as well as several secondary age-associated pathological processes. Several epidemiological and clinical studies have revealed potential roles for dietary antioxidants in age-associated autoimmune diseases, and the reduction of risk of morbidity and mortality from cancer. The Big Blue transgenic mouse mutation detection system allows the relationship between oxidative stress, mutagenesis, and carcinogenesis to be examined in a manner not previously possible. The Big Blue system will be utilized to measure the effects of dietary antioxidants on mutation frequency and pattern, and tumorigenesis under conditions of normal and elevated endogenous oxidative stress. The results may provide insight into the nature and extent of tissue-specific oxidative stress and lay the foundation for future studies to modify the incidence or progression of tumorigenesis. The results will have implications for our understanding spontaneous somatic mutation in humans and for defining the maximal antimutagenic effect of vitamin E, C and beta-carotene supplements separately or in cocktails.